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Structural Studies on Stilbene Oligomers Isolated from the Seeds of

Melinjo (Gnetum gnemon L.)
Hiroko Tani, Hiroyuki Koshino, Tohru Taniguchi, Maiko Yoshimatsu, Susumu Hikami,
and Shunya Takahashi*
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ABSTRACT: This paper describes the isolation and structural

determination of a new stilbene dimer, named 7a-epi-gnetin C,
from melinjo (Gnetum gnemon L.) seed extract. The relative
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structure was elucidated based on NMR spectroscopic evidence,

while the absolute configuration was assigned by a combination of
NMR and electronic circular dichroism spectroscopic analysis and
chemical conversion. 7a-epi-Gnetin C was evaluated as an
antioxidant and was shown to have a comparable activity to the
known stilbene oligomers. In addition, the structural revision of
gnetin L, a known stilbene dimer, was also discussed.

■ INTRODUCTION
Gnetum gnemon L. is a species of the Gnetaceae family
commonly called melinjo in Indonesia, known to be rich in
resveratrol derivatives. Its fruit and seeds are used as ordinary
food in Indonesia and their extracts have been reported to
show several pharmacological activities from in vitro to human
studies.1−6 A stilbene monomer, trans-resveratrol (8) and
stilbene oligomers such as gnetin C (4), gnemonoside A (5),
gnemonoside C (6), gnemonoside D (7), gnetin L, and gnetin
E (9) have been isolated from the fruit and/or seeds (Figure
1).1,2 The oligomers possess a 1,2-diaryldihydrobenzofuran
skeleton as a basic structural motif. The relative stereo-
chemistry of two chiral centers in the core has been assigned
by NOE experiment,1,2,7−9 whereas the absolute configuration
has been traditionally elucidated by comparison of its
electronic circular dichroism (ECD) spectrum with that of
known structures.10−12 In our ongoing search for biologically
active components from melinjo seed extract (MSE), we
isolated a new minor epimer of 4, termed 7a-epi-gnetin C (1)
along with known compounds as shown in Figure 1. In this
paper, we report the elucidation of structure 1 and structural
revision of gnetin L (2) to the regioisomer 3. In addition, a
series of resveratrol derivatives shown in Figure 1 were
submitted to the oxygen radical absorbance capacity (ORAC)
assay and evaluated as an antioxidant.
gel column chromatography, and reversed phase HPLC to give
1. The existence of 1 in the MSE was confirmed by analytical
HPLC analysis before being treated with the enzyme. The
molecular formula of 1 was established as C28H22O6 by HR-
ESI-MS spectrum (m/z: 477.1313 [M + Na]+; calcd for
C28H22O6Na, 477.1314). The 1H and 13C NMR data ensured a
set of 2,3-diaryl-dihydrobenzofuran ring and the connectivity
of units A and B supported by HMBC correlations from H-8a
to C-11b and C-12b, which indicated that 1 possessed the
same planar structure as that of 4 (Table 1). The coupling
constant between H-7a and H-8a for 1 is 8.3 Hz, whereas for 4
is reported to be 4.5 Hz.7 These values were diagnostic and the
same as the values reported for cis-dihydrobenzofuran and its
trans isomer derived from (−)-ε-viniferin,13 and the cis- and
trans-dihydrobenzofuran moieties included in suffruticosol D
from Paeonia suffruticosa,14 indicating that 1 is in a cis-form on
the dihydrofuran ring. In comparison between 1H NMR
chemical shifts of 1 (Table 1) and those of 4 (Table S3), the
cis orientation of A1 and A2 rings in 1 causes up-field shifts for
aromatic ring signals of H-2a (Δ −0.22 ppm), H-3a (Δ −0.23
ppm), H-10a (Δ −0.44 ppm), and H-12a (Δ −0.22 ppm) by
stacking effects. In addition, the NOESY correlations between

■ RESULTS AND DISCUSSION

The seeds (endosperms) of melinjo (G. gnemon L.), collected
Received: February 29, 2020
Accepted: May 5, 2020
Published: May 19, 2020
in Indonesia, were powdered and extracted with 55% aqueous
EtOH. MSE with enzymatic hydrolysis of glucosides was
successively subjected to ODS column chromatography, silica

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Figure 1. Structures of natural stilbene derivatives from G. gnemon L.

Table 1. 1H and 13
C NMR Data for 1 in Acetone-d6 The absolute configuration of 1 was determined by the
optical data comparison of a phenol derivative 10 derived from
position δC δH (J in Hz) HMBC NOE
both 1 and 4. Namely, treatment of 1 with a Pd/C catalyst
1a 129.05 under hydrogen atmosphere at room temperature underwent a
2a (6a) 129.05 7.00 (2H, d, 1a, 4a, 6a, 7a 3a (5a), 7a, reductive opening of the tetrahydrofuran ring at C-7a to give
J = 8.7 Hz) 10a (14a)
10 {[α]D25 −60.8 (c 0.02, MeOH)} (Scheme 1). Its 1H and
3a (5a) 115.1 6.61 (2H, d, 1a, 5a 2a (6a) 13
J = 8.7 Hz) C NMR data were identical with those of the reduction
4a 157.4 product prepared15 from 4, and its optical rotation was also
7a 90.3 5.85 (1H, d, 1a, 2a (6a), 9a 2a (6a), 8a nearly equal in sign and magnitude16 to that of 10 {[α]D26
J = 8.3 Hz) −66.8 (c 0.11, MeOH)} derived from 4 {[α]D25 −18.5 (c 0.1,
8a 51.7 4.56 (1H, d, 9a, 10a (14a), 7a, 10a (14a) MeOH)}, indicating that the configuration of C-8a of 1 was
J = 8.3 Hz) 11b, 12b
the same as 4. Therefore, 1 was determined to be the C-7a
9a 142.2
epimer of 4.
10a (14a) 108.6 5.73 (2H, d, 8a, 12a 2a (6a), 8a
J = 2.3 Hz) The absolute configuration of (−)-gnetin C (shown as 4 in
11a (13a) 158.7 10a (14a), 12a Figure 1) was reported to be 7aS,8aS by a vibrational circular
12a 101.6 5.99 (1H, t, 10a (14a), 11a dichroism (VCD) study.17 We independently ensured this
J = 2.3 Hz) (13a) assignment using a fully methylated benzaldehyde derivative,
1b 130.0 12 prepared from 4 via 11 (Scheme 2). This compound was
2b (6b) 128.7 7.45 (2H, d, 4b, 6b, 7b 7b, 8b designed in order to suppress the effect of hydrogen bonding18
J = 8.2 Hz)
and the free rotation of a terminal styryl unit. As expected, the
3b (5b) 116.4 6.86 (1H, d, 1b, 4b, 5b
J = 8.2 Hz) experimental ECD spectrum of 12 showed good agreement
4b 158.3 with the calculated one for (7aS,8aS)-12 at ca. 210 nm, a
7b 129.13 7.11 (1H, d, 2b (6b), 8b, 9b 2b (6b), 10b, strong positive band at ca. 245 nm, a broad negative band at ca.
J = 16.5 Hz) 14b 280 nm, and a broad positive band at ca. 325 nm (Figure 2).
8b 126.8 6.99 (1H, d, 7b, 10b, 14b 2b (6b), 10b, Meanwhile, the theoretical ECD spectrum calculated for
J = 16.5 Hz) 14b (7aR,8aS)-12 exhibited a different feature to that of the
9b 140.8 experimental one. From these results, the absolute config-
10b 99.3 6.72 (2H, d, 8b, 11b, 12b, 7b, 8b uration of the parent compound 4 was unambiguously assigned
J = 0.9 Hz) 14b
11b 162.9
as 7aS,8aS, which is consistent with the previous result.17 Thus,
12b 117.1
the absolute configuration of the new compound 1 was
13b 155.3
determined as 7aR,8aS.
14b 108.3 6.62 (2H, d, 8b, 10b, 12b, 7b, 8b
In the course of identifying other isolated compounds, we
J = 0.9 Hz) 13b found that NMR spectral data in acetone-d6 of 3 was almost
11a, 7.85 (2H, s) 10a (14a), 12a identical to those of gnetin L (2)2 with a 3-hydroxy-5-
13a-OH methoxyphenyl group. The 1H NMR spectra of the isolated 3
in acetone-d6, chemical shifts of some aromatic signals were
overlapped and second order effects were observed. To clarify
vicinal H-7a and H-8a and between two aromatic groups H-2a the substitution pattern of aromatic rings, we tried to measure
1
(6a) and H-10a (14a) further supported a cis-orientation. H NMR spectra in several solvent systems. In the 1H NMR
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Scheme 1. Preparation of 10 by Hydrogenation of 1 or 4
Scheme 2. Chemical Conversion of 4 into a Benzaldehyde Derivative 12
Figure 2. Calculated and experimental ECD spectra of 12.
Figure 3. Expanded 1H NMR spectra in comparison with spin−spin coupling patterns for 4-hydroxy-3-methoxyphenyl ring portion of 3 in acetone-
d6 (a) and CD3CN (b).
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spectra of 3 in CD3CN, the three proton signals in the A1 ring
were observed at 6.76, 6.80, and 6.92 ppm as doublet of
doublets (J = 7.8, 1.8 Hz), doublet (J = 7.8 Hz), and doublet (J
= 1.8 Hz), respectively (Figure 3). The ortho-coupling protons
at δH 6.76 and 6.80 (J = 7.8 Hz) and meta-coupling protons at
δH 6.76 and 6.92 (J = 1.8 Hz) proposed an ABX system of 4-
hydroxy-3-methoxyphenyl group for the A1 ring. In addition,
the HMBC correlation peak from the hydroxy proton signal at
δH 6.57 (1H, s) to δC 115.6 (C-5a) indicated that the hydroxy
group was attached to the C-4a position (Figure 4). Thus, we
concluded that the structure of natural gnetin L should be
revised to be the regioisomer 3. This structural revision of
gnetin L (3) revealed that gnetin L2 and the later reported
macrostachyol D by Sri-in et al. in 2011 were identical.19
Finally, we have tested the antioxidant activities of the new
as well as known compounds, as it is well known that
polyphenols have potentially high antioxidant activities.20 As
listed in Table 2, all tested compounds showed stronger ORAC
activity compared with L-ascorbic acid (Table 2). Compounds
1 and 3 were less active than 4, indicating that a change in the
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Plant Material. The seeds (endosperms) of melinjo were

collected in Indonesia (Desa Bangkok, Kecamatan Gurah
Kabupaten Kediri, Kediri, Jawa Timur) in July 2009 and have
been identified by Dr. Eishin Kato. Voucher specimens
(number 090716) have been deposited at Hosoda SHC Co.
Ltd., Fukui, Japan.
Extraction and Isolation. The preparation of MSE and
isolation of 4−7 were performed based on the modified
method reported by Kato et al.2 In brief, the powder of dried
Figure 4. HMBC correlations for 3 in CD3CN. endosperms of melinjo was extracted with 55% aqueous
ethanol, and the MSE (23.0 g) was subjected to ODS column
Table 2. ORAC Antioxidant Capacity per mol of Stilbene chromatography, silica gel column chromatography, and
Oligomers and L-Ascorbic Acida recrystallization and/or preparative HPLC to give 4 (0.19 g),
mmol 5 (1.15 g), 6 (62 mg), and 7 (0.23 g).
compound typeb TE/molc The MSE (150 g) was treated with 3 g of β-glucosidase in
7a-epi-gnetin C (1) resveratrol dimer 5081 ± 420 0.02 M citric acid (12 L) at 40 °C for 24 h. The hydrolyzed
gnetin L (3) a resveratrol unit and an 5298 ± 414 residue (120 g) was subjected to Daiso Gel column
isorhapontigenin unit chromatography (Daiso gel IR-60, 600 mm × 80 mmID)
gnetin C (4) resveratrol dimer 8597 ± 619 with 9 L (each 1 L/fraction) of 6, 12, and 25% MeOH in
gnemonoside A (5) resveratrol dimer 4679 ± 586 CHCl3 as the eluent. The fraction eluted with 25% MeOH in
gnemonoside C (6) resveratrol dimer 6336 ± 627 CHCl3 was further purified by MPLC using ODS column
gnemonoside D (7) resveratrol dimer 5663 ± 997 chromatography (Hi-Flash Column ODS-SM, 100 mm × 26
trans-resveratrol (8) resveratrol monomer 8241 ± 350 mmID, Yamazen) using aqueous MeOH (20−80%, 54 min
gnetin E (9) resveratrol trimer 2129 ± 237 linear, 100%, 10 min hold) with 0.1% TFA as the eluent at a
L-ascorbic acid
d
− 638 ± 59 flow rate of 15 mL/min (15 mL × 64). Fraction 31−33 was
a
Data are expressed as the mean ± SD of three experiments. bThis then purified by preparative HPLC using aqueous MeOH
classification was based on the structure of 8 as a monomer. cData are (48−50%, 60 min linear, 50−55%, 60 min linear, 55%, 30 min
expressed as Trolox equivalent per 1 mol sample. dL-Ascorbic acid was hold) with 0.1% TFA at a flow rate of 7.5 mL/min to give 921
used as positive control.26 (tR = 124 min, 1.82 mg ≥ 99% HPLC). Furthermore, the
hydrolyzed residue (70 g) was subjected to ODS column
stereochemistry of C-7a in A1 ring and the methoxy group at chromatography (Cosmosil 75C18-PREP, 400 mm × 80
C-3a in A1 ring decreased the activity. In addition, compounds mmID, Nacalai Tesque) with 6 L (each 1 L/fraction) of 20,
5−7 were less active than 4, indicating that glucosylation of the 40, 60, and 100% aqueous MeOH. The third and fourth
hydroxyl group at C-4a in A1 ring and at C-4b in B1 ring fractions eluted with 40% aqueous MeOH were subjected to
decreased the activity. Although the glucosyl substitution MPLC using ultra pack silica gel column (300 mm × 37
effects of the hydroxyl group in A1 and B1 ring on DPPH mmID, Yamazen) with MeOH (10%, 15 min hold, 10−20%,
radical scavenging activity reported by Kato et al. in 2009 were 45 min linear, 20−50%, 45 min linear, 50%, 60 min hold) in
very small, the number and position of free phenolic hydroxyl CHCl3 as the eluent at a flow rate of 20 mL/min (20 mL ×
groups in the molecule will contribute to the antioxidant 120). Fraction 27−30 was further purified by preparative
activity as well as other polyphenols. Furthermore, the activity HPLC using aqueous MeOH (43−46%, 30 min linear, 46%,
of 9 was 4-fold less active than 4 and 8. This suggested that a 150 min hold) with 0.1% TFA at a flow rate of 7.5 mL/min to
molecule larger than a dimer is less effective as an antioxidant. give fractions that eluted at 117 and 133 min to give 1 (1.82

■ METHODS
General Procedures. All melting points were determined
with a Yanaco MP-500 apparatus and are uncorrected. Optical
rotations were measured using a JASCO DIP-370 digital
polarimeter. IR spectra were recorded by the attenuated total
reflection method using ZnSe prism on a JASCO VALOR-III
spectrophotometer. 1H and 13C NMR spectra were recorded at
500 and 125 MHz or 600 and 150 MHz with Agilent
Technologies V500 or JEOL ECA600 spectrometers. Chemical
shifts were referenced to a residual signal (1H) and a solvent
signal (13C) of CD3CN (δH 1.93, δC 118.3), acetone-d6 (δH
2.04, δC 29.8), CD3OD (δH 3.30, δC 49.0), and CDCl3 (δH
7.26, δC 77.0). ESIMS were recorded on a JEOL JMS-T100LC
mass spectrometer. Preparative HPLC was conducted on a
Waters 600E system with a Cosmosil 5C18-AR-II column (250
mm × 20 mmID, Nacalai Tesque). Medium-pressure liquid
chromatography (MPLC) was carried out on a Yamazen
MPLC system. Merck precoated silica gel 60 F254 plates, 0.25
mm in thickness, were used for analytical thin-layer
chromatography.
12248
mg ≥ 99% HPLC) and 3 (3.59 mg ≥ 99% HPLC),
respectively.
7a-epi-Gnetin C (1): [α]D26 + 201 (c 0.11, MeOH); IR
(ZnSe) νmax: 3235, 2932, 2840, 1670, 1595, 1509, 1448, 1429,
1251, 1194, 1142, 998, 821, and 799 cm−1; 1H and 13C NMR
(600 and 150 MHz, acetone-d6), see Table 1; HRESIMS m/z:
477.1313 [M + Na]+ (calcd for C28H22O6Na, 477.1314).
Gnetin L (3): 1H and 13C NMR (600 and 150 MHz,
CD3CN), see Table S2.
Gnetin E (9): 1H and 13C NMR (600 and 150 MHz,
acetone-d6), see Table S2.
Analysis of Resveratrol Derivatives. Analysis of
resveratrol derivatives in MSE was performed by the
Prominence HPLC system (Shimadzu) with a Cosmosil
5C18-AR-II column (250 mm × 4.6 mmID, Nacalai Tesque),
following the analysis conditions previously reported.22 The
contents of dimer derivatives in MSE were as follows: 1.5 mg/g
1, 2.2 mg/g 3, 28 mg/g 4, 101 mg/g 5, 16 mg/g 6, 48 mg/g 7,
and 0.3 mg/g 8.
(S)-2-(1-(3,5-Dihydroxyphenyl)-2-(4-hydroxyphenyl)-
ethyl)-5-(4-hydroxyphenethyl)benzene-1,3-diol (10).
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From 4. To a stirred solution of gnetin C (10.2 mg, 22.4 μmol)
in ethyl acetate (2.0 mL) was added 10% Pd/C (16.1 mg).
The mixture was stirred vigorously under a hydrogen
atmosphere at room temperature (rt) for 22 h, filtered through
a pad of Celite, and then concentrated. The residue was
purified by preparative TLC (dichloromethane/methanol =
10:1, 3 developments) to give 10 (7.0 mg, 68%) as an
amorphous solid: [α]D26 −66.8 (c 0.11, MeOH); IR (ZnSe)
νmax: 3200, 2920, 2843, 1590, 1510, 1423, 1240, 1219, 1142,
1000, and 818 cm−1; 1H NMR (500 MHz, CD3OD): δ 6.95
(2H, d, J = 8.6 Hz), 6.91 (2H, d, J = 8.6 Hz), 6.65 (2H, d, J =
8.6 Hz), 6.55 (2H, d, J = 8.6 Hz), 6.46 (2H, brd, J = 2.2 Hz),
6.04 (2H, s), 6.02 (1H, t, J = 2.2 Hz), 4.65 (1H, dd, J = 9.5, 6.6
Hz), 3.53 (1H, dd, J = 13.4, 9.5 Hz), 3.26 (1H, dd, J = 13.4,
6.6 Hz), 2.74−2.66 (2H, m), and 2.59−2.55 (2H, m); 13C
NMR (150 MHz, CD3OD): δ 158.5, 157.6, 156.3, 155.7,
149.6, 142.2, 134.6, 134.3, 130.9, 130.4, 116.2, 116.0, 115.4,
108.34, 108.26, 100.6, 43.4, 39.3, 38.5, and 38.1; HRESIMS
m/z: 481.1620 [M + Na]+ (calcd for C28H26O6Na, 481.1627).
From 1. To a stirred solution of 1 (1.10 mg, 2.42 μmol) in
methanol (0.5 mL) was added 10% Pd/C (2.5 mg). The
mixture was stirred vigorously under a hydrogen atmosphere at
rt for 9 h, filtered through a pad of Celite, and then
concentrated. The residue was purified by preparative TLC
(dichloromethane/methanol = 10:1, 5 developments) to give
10 (0.61 mg, 55%) as an amorphous solid whose spectral data
were identical with those of an authentic sample derived from
gnetin C: [α]D25 −60.8 (c 0.02, MeOH); HRESIMS m/z:
481.1627 (calcd for C28H26O6Na [M + Na]+, 481.1627).
Permethylation of Gnetin C (11). To a stirred
suspension of 4 (10.4 mg, 22.9 μmol) and potassium carbonate
(61 mg, 441 μmol) in acetone (0.5 mL) was added methyl
iodide (27.4 μL, 441 μmol), and the mixture was stirred under
reflux for 2 h. More methyl iodide (27.4 μL, 441 μmol) and
acetone (0.5 mL) were added and the reaction was further
continued for 3 h. After cooling to rt, the reaction mixture was
concentrated, diluted with dichloromethane/methanol (20:1),
filtered through a pad of Celite, and then concentrated. The
residue was purified by preparative TLC (n-hexane/ethyl
acetate = 2:1, 3 developments) to give 11 (11.2 mg, 97%) as
an amorphous solid: [α]D27 + 1.2 (c 0.41, CHCl3); IR (ZnSe)
νmax: 2920, 2820, 1583, 1505, 1453, 1420, 1241, 1165, 1150,
1023, 821, and 741 cm−1; 1H NMR (500 MHz, CDCl3), see
Table S3; 13C NMR (125 MHz, CDCl3): δ 161.6, 160.8, 159.4,
159.3, 156.9, 145.2, 140.3, 133.9, 130.0, 128.4, 127.8, 126.9,
126.8, 115.2, 114.1, 113.9, 105.5, 102.5, 100.4, 98.6, 92.8, 55.7,
55.4, 55.3, and 55.2; HRESIMS m/z: 547.2095 [M + Na]+
(calcd for C33H32O6Na, 547.2097).
(2S,3S)-3-(3,5-Dimethoxyphenyl)-4-methoxy-2-(4-
methoxyphenyl)-2,3-dihydrobenzofuran-6-carbalde-
hyde (12). To a stirred solution of 11 (11.0 mg, 21.0 μmol) in
tetrahydrofuran (0.5 mL) and water (0.2 mL) was added
dropwise a solution of OsO4 (ca. 5 μmol) in 2-methyl-2-
propanol (50 μL) at rt. After stirring for few minutes, NaIO4
(43 mg, 0.20 mmol) was added by portions. After being stirred
for an additional 3 h, the mixture was filtered through a pad of
Celite. The filtrate was diluted with ethyl acetate, washed
successively with aqueous Na2S, water, and brine, dried, and
concentrated. The residue was purified by preparative TLC (n-
hexane/ethyl acetate = 4:1, 3 developments) to give 12 (7.0
mg, 80%) as an amorphous solid: [α]D26 + 106.4 (c 0.23,
CHCl3); IR (ZnSe) νmax: 2920, 2808, 1685, 1585, 1508, 1450,
1420, 1195, 1150, 1080, 1060, 820, and 745 cm−1; 1H NMR
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(500 MHz, CDCl3), see Table S3; 13C NMR (125 MHz,
CDCl3): δ 191.6, 161.5, 160.9, 159.7, 157.3, 144.2, 139.1,
133.2, 126.8, 123.0, 114.1, 105.6, 105.3, 104.3, 98.7, 93.2, 55.7,
55.6, and 55.3; HRESIMS m/z: 443.1473 [M + Na]+ (calcd
for C25H24O6Na, 443.1471).
ECD Calculation. ECD calculations of (7aS,8aS)-12 were
initiated with a preliminary MMFF conformational search on a
Spartan’10 program.23 The lower energy conformers within 2.4
kcal/mol from the most stable were optimized at the DFT/
B3LYP/6-31G(d) level using a Gaussian 09 program.24 The
resultant stable conformers within 2.0 kcal/mol, from the most
stable ones, were further submitted to a DFT/B3LYP/6-
311G(d,p) optimization considering the solvent effects. The
ECD spectra of the obtained 10 conformers within 1.0 kcal/
mol, from the most stable ones, were calculated at the
TDDFT/B3LYP/6-311G(d,p) level. The first 55 singlet →
singlet electronic transitions were considered. The calculated
ECD spectra in Δε unit were obtained by using Gaussian band
shapes with 0.15 eV half-width at 1/e of peak height.
ORAC Assay. The ORAC analysis has been performed
following the method25 reported by Shimizu et al. with minor
modifications. In brief, a sample was dissolved directly in an
ethanol/water mixture (50:50, v/v) and diluted with
phosphate buffer (75 mM, pH 7.4). The sample solution (20
μL) was transferred to a 96-well microplate, and then
fluorescein (200 μL, 94.4 nM) and AAPH (75 μL, 63.4
mM) were added and mixed. Phosphate buffer (75 mM, pH
7.4) was used as a blank solution, and Trolox as the standard
solution. The assay was carried out on a FLUOstar OPTIMA
plate reader utilizing fluorescence filters with 485 nm excitation
and 520 nm emission. The antioxidant capacity of the sample
was calculated as mmol Trolox equivalent per mol (mmol TE/
mol).
■ ASSOCIATED CONTENT
* Supporting Information
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acsomega.0c00910.
1
H and 13C NMR spectra for 1, 3, 10, 11, and 12; FT-IR
and MS spectra for 1; and NMR data for 3, 4, 9, 11, and
12 (PDF)
■ AUTHOR INFORMATION
Corresponding Author
Shunya Takahashi − RIKEN Center for Sustainable Resource
Science, Saitama 351-0198, Japan; orcid.org/0000-0001-
9148-9814; Phone: +81-484-67-9223; Email: shunyat@
riken.jp; Fax: +81-484-62-4627
Authors
Hiroko Tani − Institute for Bee Products & Health Science,
Yamada Bee Company, Inc., Kagamino, Okayama 708-0393,
Japan; orcid.org/0000-0003-4444-8248
Hiroyuki Koshino − RIKEN Center for Sustainable Resource
Science, Saitama 351-0198, Japan
Tohru Taniguchi − Graduate School of Advanced Life Science,
Frontier Research Center for Post-Genome Science and
Technology, Hokkaido University, Sapporo 001-0021, Japan;
orcid.org/0000-0002-4965-7383
Maiko Yoshimatsu − Institute for Bee Products & Health
Science, Yamada Bee Company, Inc., Kagamino, Okayama 708-
0393, Japan
https://dx.doi.org/10.1021/acsomega.0c00910
ACS Omega 2020, 5, 12245−12250
ACS Omega http://pubs.acs.org/journal/acsodf Article

Susumu Hikami − Institute for Bee Products & Health Science,
Yamada Bee Company, Inc., Kagamino, Okayama 708-0393,
Japan
Complete contact information is available at:
https://pubs.acs.org/10.1021/acsomega.0c00910
Notes
The authors declare no competing financial interest.
(16) Compound 1 seemed to not be an enantiomerically pure by
comparison of the specific rotation value although the purity was not
determined by HPLC analyses using a chiral column.
(17) Buffeteau, T.; Cavagnat, D.; Bisson, J.; Marchal, A.; Kapche, G.
D.; Battistini, I.; Da Costa, G.; Badoc, A.; Monti, J.-P.; Mérillon, J.-M.;
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ACKNOWLEDGMENTS (19) Sri-in, P.; Sichaem, J.; Siripong, P.; Tip-pyang, S. Macro-
stachyols A−D, new oligostilbenoids from the roots of Gnetum
We thank Dr. T. Nakamura for expert LC−MS analysis and
macrostachyum. Fitoterapia 2011, 82, 460−465.
Dr. A.-M. Oprea for proofreading the manuscript. (20) Ishimoto, H.; Tai, A.; Yoshimura, M.; Amakura, Y.; Yoshida, T.;

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